Photo Credit: jitendrajadhav
The following is a summary of “CNS Relapse in High-Grade B-cell Lymphoma with MYC and BCL2 Rearrangements and Dark-Zone Signature-Expressing DLBCL,” published in the October 2024 issue of Hematology by Alduaij et al.
High-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL-DH-BCL2), also known as ‘double-hit lymphoma,’ is strongly associated with an increased risk of central nervous system (CNS) relapse. Historical estimates of this risk may be compromised due to selection bias. The dark-zone gene expression signature (DZsig), initially identified in HGBCL-DH-BCL2 tumors, is crucial in understanding diffuse large B-cell lymphoma (DLBCL) morphology.
Researchers conducted a retrospective study assessing CNS relapse rates in people with HGBCL-DH-BCL2 from a population-based cohort with comprehensive fluorescence in situ hybridization testing. The study also explored the CNS relapse risk in DLBCL tumors expressing the DZsig, independent of HGBCL-DH-BCL2 status.
They included individuals with HGBCL-DH-BCLW and DLBL morphology tumors, performed fluorescence in situ hybridization, and applied the “refined cell of origin” classification to identify DZsig+ tumors. CNS servers’ risk was compared between groups and further stratified by the CNS International Prognostic Index (CNS-IPI) and concordant bone marrow involvement.
The results showed that the 2-year CNS relapse risk for people with HGBCL-DH-BCL2 was 6.8%, with most relapses occurring early with being leptomeningeal (73%), often co-occurring with systemic relapse (64%). High CNS-IPI scores and concordant bone marrow involvement were linked to increased CNS relapse risk in HGBCL-DH-BCL2. Among DLBCL patients, 20% of tumors with a germinal cancer B-cell-like phenotype (GCB-DLBCL) were classified as DZsig+, which had a 2-year CNS relapse risk of 6.4%. In contrast, DZsig-negative GCB-DLBCL had a lower 2-year relapse risk (1.4%, P=0.04) and showed exclusively parenchymal relapses.
Investigators concluded that the CNS relapse risk in HGBCL-DH-BCL2 is lower than earlier. Reports suggested DZsig+ tumors help refine risk stratification in GCB-DLBCL, offering better insight into CNS relapse potential.
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